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Pyrazole permethrin-induced liver toxicity in mice involves the PI3K/AKT/NF-κB pathway: Integrated network
Jingjing Chen1, Bin Liu2, Yuanyuan Li3
1Department of Thoracic Surgery, The Affiliated Hospital of Kangda College of Nanjing Medical University (The Ganyu District People's Hospital of Lianyungang City), Lianyungang 222100, China; Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, China.
Pyraclostrobin (PP) fungicide exposure causes liver injury in mice by inducing oxidative stress and inflammation. This study identifies key molecular targets and pathways, highlighting risks of subacute exposure for agricultural safety standards.
Area of Science:
- Environmental Toxicology
- Molecular Toxicology
- Biochemistry
Background:
- Pyraclostrobin (PP) is a widely used, stable, fat-soluble fungicide.
- Environmental accumulation and bioaccumulation of PP pose potential health risks.
- Understanding PP-induced liver injury is crucial for public health and agricultural safety.
Purpose of the Study:
- To systematically elucidate pyraclostrobin-induced liver injury using network toxicology and in vitro/in vivo methods.
- To identify key molecular targets and signaling pathways involved in PP hepatotoxicity.
- To assess the risks associated with subacute PP exposure.
Main Methods:
- Network toxicology to identify potential targets and core genes.
- In vitro and in vivo (mouse models) investigations.
- Histopathological analysis, serum biochemistry, oxidative stress markers, and inflammatory cytokine analysis.
Main Results:
- Network toxicology identified 328 potential targets and 12 core genes.
- Histopathology revealed hepatocyte necrosis and inflammation.
- PP exposure induced oxidative stress (decreased antioxidant enzymes, increased MDA) and inflammation (elevated IL-1β, TNF-α) via the PI3K/AKT/NF-κB axis.
Conclusions:
- Subacute pyraclostrobin exposure causes significant liver injury in mice.
- Oxidative stress and inflammation are key mechanisms underlying PP-induced hepatotoxicity.
- Safety standards for agricultural use of PP must consider subacute exposure risks.
